Per2蛋白抑制β<sub>1</sub>-肾上腺素受体自身抗体诱导的心肌细胞死亡

李朋佳; 贾微微; 陆洁蓓; 马明霞; 周秀雅; 王宁; 原媛; 郭蕊; 牛晓辰; 王晓晖; 王丽

doi:10.16016/j.2097-0927.202110010

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Per2蛋白抑制β₁-肾上腺素受体自身抗体诱导的心肌细胞死亡

基础医学 | 更新时间：2026-02-13

- Per2蛋白抑制β₁-肾上腺素受体自身抗体诱导的心肌细胞死亡
- Period 2 protein inhibits cardiomyocyte death induced by β₁-adrenoceptor autoantibodies
- 陆军军医大学学报 2022年44卷第9期页码：898-905
- 作者机构：
  
  1.030001 太原，山西医科大学基础医学院：基础医学研究中心
  2.030001 太原，山西医科大学基础医学院：形态学实验室
  3.030012 太原，山西医科大学附属人民医院
- 作者简介：
  
  [王丽，E-mail：mirror0117@126.com WANG Li, E-mail: mirror0117@126.com
- 基金信息：
  
  国家自然科学基金面上项目(31871177);山西省研究生教育创新项目(2021Y409)
- DOI：10.16016/j.2097-0927.202110010
  中图分类号： R322.11;R329.25;R341
- 收稿：2021-10-07，
  
  修回：2021-12-08，
  
  纸质出版：2022-05-15
- 稿件说明：
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李朋佳, 贾微微, 陆洁蓓, 等. Per2蛋白抑制β₁-肾上腺素受体自身抗体诱导的心肌细胞死亡[J]. 陆军军医大学学报, 2022,44(9):898-905.

Pengjia LI, Weiwei JIA, Jiebei LU, et al. Period 2 protein inhibits cardiomyocyte death induced by β₁-adrenoceptor autoantibodies[J]. Journal of Army Medical University, 2022, 44(9): 898-905.
李朋佳, 贾微微, 陆洁蓓, 等. Per2蛋白抑制β₁-肾上腺素受体自身抗体诱导的心肌细胞死亡[J]. 陆军军医大学学报, 2022,44(9):898-905. DOI： 10.16016/j.2097-0927.202110010.

Pengjia LI, Weiwei JIA, Jiebei LU, et al. Period 2 protein inhibits cardiomyocyte death induced by β₁-adrenoceptor autoantibodies[J]. Journal of Army Medical University, 2022, 44(9): 898-905. DOI： 10.16016/j.2097-0927.202110010.

摘要

目的

探讨周期蛋白2(period 2，Per2)在β

-肾上腺素受体(β

-adrenergic receptor，β

-AR)自身抗体(β

-adrenergic receptor autoantibodies，β

-AA)诱导的心肌细胞死亡中的作用。

方法

选取6~8周龄SD雄性大鼠16只随机分为主动免疫组[模型组，采用β

-肾

上腺素受体细胞外第二环抗原肽段(β

-AR-EC Ⅱ)对大鼠进行主动免疫

]

和对照组(同期注射Na

等溶液)，每组8只。8周时取大鼠血清，提纯β

-AA。购买H9c2心肌细胞，随机分为Control组、β

-AA组和β

-AR+β

-AA组，CCK-8法检测细胞存活率(

=8)；Control组和β

-AA(1 μmol/L)组细胞经地塞米松同步化4 h后，Western blot检测两组不同时间点心肌细胞Per2的表达，JTK_CYCLE分析昼夜节律参数(

=11)；分别采用慢病毒shPer2和Per2敲低或过表达心肌细胞中Per2的表达，RT-PCR和Western blot检测Per2的表达(

=6)；在慢病毒敲低Per2(

=8)和过表达Per2(

=10)基础上，结合β

-AA处理，CCK-8法检测心肌细胞存活率。

结果

CCK-8结果显示，β

-AA诱导H9c2细胞存活率明显降低(

0.05)。Western blot结果显示β

-AA显著抑制心肌细胞Per2蛋白的节律性表达(JTK_CYCLE

0.05)，其中CT8和CT16降低最为明显(

0.01)。慢病毒敲低Per2表达可引起心肌细胞存活率降低；在此基础上进行β

-AA处理，细胞存活率进一步降低(

0.001)。而过表达Per2可明显逆转β

-AA诱导的心肌细胞存活率下降(

0.001)。

结论

Per2抑制β

-AA诱导的H9c2心肌细胞死亡。

Abstract

Objective

To investigate the role of period 2 (Per2) protein in the death of cardiomyocytes induced by β

-adrenergic receptor autoantibodies (β

-AA).

Methods

Sixteen male SD rats aged 6~8 weeks were randomly divided into active immunization (model) group and control group (

=8). The model group was immunized with the second extracellular loop of beta1-adrenoceptor (β

-AR-EC Ⅱ)

and the control group was injected with Na

and other solutions. The rat serum was subsequently collected at 8 weeks

followed by the purification of β

-AA. H9c2 cardiomyocyte were selected and randomly divided into control group

-AA group

and β

-AR+β

-AA group. Cell viability of each group was detected by CCK-8 assay (

=8). Then H9c2 cells in th

e control group and β

-AA 1 μmol/L group were synchronized with dexamethasone for 4 h

the expression of Per2 in cardiomyocytes at different circadian time (CT) points was measured by Western blotting

and JTK_CYCLE was used to analyze the circadian rhythm parameters (

=11). Moreover

Per2 in H9c2 cells was knocked down or overexpressed by lentiviral shPer2 and lentiviral Per2

respectively; RT-PCR and Western blotting were performed to detect the changes of Per2 expression (

=6). On the basis of knockdown (

=8) or overexpression (

=10) of Per2

the H9c2 cells were further treated with β

-AA

and the cell survival rate was tested by CCK-8 assay.

Results

CCK-8 assay showed that the survival rate of H9c2 cells was significantly decreased after β

-AA treatment (

0.05). Western blotting demonstrated that β

-AA remarkably inhibited the rhythmic expression of Per2 protein in the cardiomyocytes (JTK_CYCLE

0.05)

with the decrease at CT8 and CT16 most obviously (

0.01). Knockdown of Per2 expression reduced the survival rate of cardiomyocytes

which was further lowered after β

-AA treatment (

0.001). However

overexpression of Per2 notably reversed the decline in H9c2 survival rate induced by β

-AA (

0.001).

Conclusion

Per2 protein inhibits β

-AA induced H9c2 cardiomyocyte death.

关键词

Keywords

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Per2蛋白抑制β1-肾上腺素受体自身抗体诱导的心肌细胞死亡

Period 2 protein inhibits cardiomyocyte death induced by β1-adrenoceptor autoantibodies

DOI：10.16016/j.2097-0927.202110010

摘要

Abstract

关键词

Keywords

references

Per2蛋白抑制β₁-肾上腺素受体自身抗体诱导的心肌细胞死亡

Period 2 protein inhibits cardiomyocyte death induced by β₁-adrenoceptor autoantibodies